Dataset Information

Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart.

ABSTRACT: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle.Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis.In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens ?1(I), ?2(I), ?1(III), and ?2(IV) as well as hydroxyproline. Alcohol also increased ?-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-? was detected. The mRNA and protein content for other ECM components, such as integrin-?5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-?3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-? and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle.These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.

SUBMITTER: Steiner JL

PROVIDER: S-EPMC4702067 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart.

Steiner Jennifer L JL Pruznak Anne M AM Navaratnarajah Maithili M Lang Charles H CH

Alcoholism, clinical and experimental research 20150624 8

<h4>Background</h4>The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle.<h4> ...[more]

PMID: 26108259

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Project description:Existing data suggest the extracellular matrix (ECM) of vertebrate skeletal muscle consists of several morphologically distinct layers: an endomysium, perimysium, and epimysium surrounding muscle fibers, fascicles, and whole muscles, respectively. These ECM layers are hypothesized to serve important functional roles within muscle, influencing passive mechanics, providing avenues for force transmission, and influencing dynamic shape changes during contraction. The morphology of the skeletal muscle ECM is well described in mammals and birds; however, ECM morphology in other vertebrate groups including amphibians, fish, and reptiles remains largely unexamined. It remains unclear whether a multilayered ECM is a common feature of vertebrate skeletal muscle, and whether functional roles attributed to the ECM should be considered in mechanical analyses of non-mammalian and non-avian muscle. To explore the prevalence of a multilayered ECM, we used a cell maceration and scanning electron microscopy technique to visualize the organization of ECM collagen in muscle from six vertebrates: bullfrogs (Lithobates catesbeianus), turkeys (Meleagris gallopavo), alligators (Alligator mississippiensis), cane toads (Rhinella marina), laboratory mice (Mus musculus), and carp (Cyprinus carpio). All muscles studied contained a collagen-reinforced ECM with multiple morphologically distinct layers. An endomysium surrounding muscle fibers was apparent in all samples. A perimysium surrounding groups of muscle fibers was apparent in all but carp epaxial muscle; a muscle anatomically, functionally, and phylogenetically distinct from the others studied. An epimysium was apparent in all samples taken at the muscle periphery. These findings show that a multilayered ECM is a common feature of vertebrate muscle and suggest that a functionally relevant ECM should be considered in mechanical models of vertebrate muscle generally. It remains unclear whether cross-species variations in ECM architecture are the result of phylogenetic, anatomical, or functional differences, but understanding the influence of such variation on muscle mechanics may prove a fruitful area for future research.

Dataset Information

Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart.

Publications

Alcohol Differentially Alters Extracellular Matrix and Adhesion Molecule Expression in Skeletal Muscle and Heart.

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